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Magnetic Resonance Materials in Physics, Biology and Medicine
Published in: Magnetic Resonance Materials in Physics, Biology and Medicine 1/2003

01-02-2003 | Research Article

Reduced glutamate neurotransmission in patients with Alzheimer's disease–an in vivo 13C magnetic resonance spectroscopy study

Authors: Alexander P. Lin, Frederick Shic, Cathleen Enriquez, Brian D. Ross

Published in: Magnetic Resonance Materials in Physics, Biology and Medicine | Issue 1/2003

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Abstract

Cognitive impairment in Alzheimer's disease (AD) is not fully explained. PET indicates reduced cerebral metabolic rate for glucose. Since glutamate neurotransmission (GNT) consumes more than 80% of the ATP generated from metabolism, a pilot study was carried out to determine the neuronal tricarboxylic acid cycle (TCA) based on the hypothesis that reduced GNT could contribute to cognitive impairment in AD.
Three AD patients with cognitive impairment (mini-mental state exam: 24 vs 30, P<0.05) and significant reduction in both N-acetyl aspartate (NAA)/Creatine (Cr) (P<0.009) and NAA/myo-inositol (mI) ratio (P<0.01), and three age-matched controls each received 0.014–0.016 g/kg/min 99%1–13C glucose IV. Quantitative 1H and proton-decoupled 13C MR brain spectra were acquired from combined posterior-parietal white matter and posterior-cingulate gray matter every 5 min for 140 min.
13C magnetic resonance spectroscopy (MRS) measures of glucose oxidation and neuronal TCA rate, including prolonged time to 13C enrichment of glutamate (Glu2) (P<0.004) and bicarbonate (HCO3) (P<0.03) as well as reduced relative enrichment of Glu2/Glu4 between 60 and 100 min (P<0.04), were significantly different in AD patients vs. controls. 13C measures of GNT, glutamine (Gln)2/Glu2 (P<0.02) and rates of glutamate enrichment (Glu2/glucose: 0.34 vs 0.86, P=ns and Glu4/glucose 0.26 vs 0.83, P=ns), were also reduced.
13C MRS measures of neuronal TCA cycle, glucose oxidation and GNT were significantly correlated with measures of neuronal integrity: NAA/Cr, [NAA] and mI/NAA as determined by 1H MRS (R 2=0.73–0.95; P<0.05–0.01), suggesting that impairment of GNT may be a contributing factor in the cognitive impairment characteristic of AD.
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Metadata
Title
Reduced glutamate neurotransmission in patients with Alzheimer's disease–an in vivo 13C magnetic resonance spectroscopy study
Authors
Alexander P. Lin
Frederick Shic
Cathleen Enriquez
Brian D. Ross
Publication date
01-02-2003
Publisher
Springer-Verlag
Published in
Magnetic Resonance Materials in Physics, Biology and Medicine / Issue 1/2003
Print ISSN: 0968-5243
Electronic ISSN: 1352-8661
DOI
https://doi.org/10.1007/s10334-003-0004-x

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